ATF3-Dependent Regulation of EGR1 in vitro and in vivo

ORL J Otorhinolaryngol Relat Spec. 2017;79(5):239-250. doi: 10.1159/000478937. Epub 2017 Aug 12.

Abstract

Background/aims: Activating transcription factor 3 (ATF3) and early growth response protein 1 (EGR1) are reported to interact, but their use as prognostic factors in cancer is discussed controversially.

Methods: We measured ATF3 and EGR1 gene expression changes in human mini-organ cultures (MOCs) of healthy nasal epithelia, UM-SCC-22B, and FADUDD cells after acid reflux exposure. Next, ATF3 and EGR1 gene expression was analysed in tumour tissues and related to the median expression of autologous reference tissue samples.

Results: ATF3 and EGR1 mRNA expression was significantly reduced after consecutive exposure of MOCs at pH <7.0 to artificial gastric juice (refluxate). In contrast, ATF3 mRNA was upregulated significantly within the first hour of incubation. EGR1 mRNA exhibited no significant changes. The analysed cell lines exhibited a cell line-specific alteration. In FADUDD cells, the upregulation of EGR1 was significant after refluxate exposure, but in HN-SCC 22B, no significant changes were detected. The analysis of the HNSCC samples confirmed the heterogeneous data of the literature.

Conclusion: The data maintain the hypothesis that ATF3 and EGR1 are involved in the beginning of inflammatory processes. Whether these two transcription factors act as tumour suppressors or promoters is context dependent and warrants analysis in further studies.

Keywords: Activating transcription factor 3; Early growth response protein 1; HNSCC; Human mini-organ culture model; Laryngopharyngeal reflux.

MeSH terms

  • Activating Transcription Factor 3 / metabolism*
  • Blotting, Western
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / metabolism*
  • Cell Line, Tumor
  • Early Growth Response Protein 1 / metabolism*
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / metabolism*
  • Humans
  • Laryngopharyngeal Reflux / complications*
  • Real-Time Polymerase Chain Reaction
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • ATF3 protein, human
  • Activating Transcription Factor 3
  • EGR1 protein, human
  • Early Growth Response Protein 1